Associations Among Environmental Exposures and Physical and Psychiatric Symptoms in a Care-Seeking Sample of U.S. Military Veterans.

Introduction: Recent research and policy (e.g., the Sergeant First Class (SFC) Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act) have highlighted the potential health consequences of toxic environmental exposures.

High executive functioning is associated with reduced posttraumatic stress after trauma exposure among male U.S. military personnel.

Introduction: Evidence suggests that executive function (EF) may play a key role in development of PTSD, possibly influenced by factors such as trauma type and timing. Since EF can be improved through intervention, it may be an important target for promoting resilience to trauma exposure. However, more research is needed to understand the relation between trauma exposure, EF, and PTSD.

Effects of total sleep deprivation on sensorimotor gating in humans.

Sensorimotor gating is a measure of pre-attentional information processing and can be measured by prepulse inhibition (PPI) of the startle reflex. Sleep deprivation has been shown to disrupt PPI in animals and humans, and has been proposed as an early phase 2 model to probe antipsychotic efficacy in heathy humans. To further investigate the reliability and efficacy of sleep deprivation to produce PPI deficits we tested the effects of total sleep deprivation (TSD) on PPI in healthy controls in a highly controlled sleep laboratory environment.

Pre-deployment threat learning predicts increased risk for post-deployment insomnia: Evidence from the Marine Resiliency Study.

Insomnia is a common and impairing consequence of military deployment, but little is known about pre-deployment risk factors for post-deployment insomnia. Abnormal threat learning tendencies are commonly observed in individuals with insomnia and maladaptive responses to stress have been implicated in the development of insomnia, suggesting that threat learning could be an important risk factor for post-deployment insomnia. Here, we examined pre-deployment threat learning as a predictor of post-deployment insomnia and the potential mechanisms underlying this effect.

Prospective longitudinal assessment of sensorimotor gating as a risk/resiliency factor for posttraumatic stress disorder.

Little is understood about cognitive mechanisms that confer risk and resiliency for posttraumatic stress disorder (PTSD). Prepulse Inhibition (PPI) is a measure of pre-attentional response inhibition that is a stable cognitive trait disrupted in many neuropsychiatric disorders characterized by poor behavioral or cognitive inhibition, including PTSD. Differentiating between PTSD-related phenotypes that are pre-existing factors vs.

Prospective examination of pre-trauma anhedonia as a risk factor for post-traumatic stress symptoms.

Background: Anhedonia, the reduction of pleasure and reward-seeking behaviour, is a transdiagnostic symptom with well-described neural circuit mediators. Although typically observed during disease state, extant hypotheses suggest that anhedonia may also be an early risk factor for development of psychopathology. Understanding the contribution of anhedonia to the trauma-response trajectory may bolster inferences about biological mechanisms contributing to pre-trauma risk versus trauma-related symptom expression, knowledge of which could aid in targeted interventions.

Dissociable impact of childhood trauma and deployment trauma on affective modulation of startle.

Trauma disorders are often associated with alterations in aversive anticipation and disruptions in emotion/fear circuits. Heightened or blunted anticipatory responding to negative cues in adulthood may be due to differential trauma exposure during development, and previous trauma exposure in childhood may also modify effects of subsequent trauma in adulthood. The aim of the current investigation was to examine the contributions of childhood trauma on affective modulation of startle before and after trauma exposure in adulthood (a combat deployment).

Sleep disturbance at pre-deployment is a significant predictor of post-deployment re-experiencing symptoms.

: Insomnia is common in service members and associated with many mental and physical health problems. Recently, longitudinal data have been used to assess the impact of disturbed sleep on mental health outcomes. These studies have consistently shown relationships between sleep disturbance and development of mental illness.

Characterizing the neural circuitry associated with configural threat learning.

Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding.

A Review of the Relationship Between Emotional Learning and Memory, Sleep, and PTSD.

Purpose Of Review: The emotional memory and learning model of PTSD posits maladaptive fear conditioning, extinction learning, extinction recall, and safety learning as central mechanisms to PTSD. There is increasingly convincing support that sleep disturbance plays a mechanistic role in these processes. The current review consolidates the evidence on the relationships between emotional memory and learning, disturbed sleep, and PTSD acquisition, maintenance, and treatment.

REM sleep and safety signal learning in posttraumatic stress disorder: A preliminary study in military veterans.

Background: Posttraumatic Stress Disorder (PTSD) is associated with a number of negative physical and mental health consequences. Fear conditioning plays an important mechanistic role in PTSD, and PTSD patients also show deficits in safety signal learning. Sleep, particularly REM sleep, is linked to improved safety learning and extinction processes in animal models and healthy humans.

Individual variation in working memory is associated with fear extinction performance.

PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory.

The Future of Contextual Fear Learning for PTSD Research: A Methodological Review of Neuroimaging Studies.

There has been a great deal of recent interest in human models of contextual fear learning, particularly due to the use of such paradigms for investigating neural mechanisms related to the etiology of posttraumatic stress disorder. However, the construct of "context" in fear conditioning research is broad, and the operational definitions and methods used to investigate contextual fear learning in humans are wide ranging and lack specificity, making it difficult to interpret findings about neural activity. Here we will review neuroimaging studies of contextual fear acquisition in humans.

COMT val158met polymorphism links to altered fear conditioning and extinction are modulated by PTSD and childhood trauma.

Background: Risk for posttraumatic stress disorder (PTSD) is thought to be mediated by gene × environment (G × E) interactions that affect core cognitive processes such as fear learning. The catechol-O-methyltransferase (COMT) val158met polymorphism has been associated with risk for PTSD and impaired fear inhibition. We used a large, relatively homogenous population to (1) replicate previous findings of poor fear inhibition in COMT Met/Met carriers with PTSD; (2) determine if COMT association with fear inhibition is moderated by childhood trauma (CT), an environmental risk factor for PTSD; and (3) determine if COMT is associated with altered fear processes after recent exposure to combat trauma.

Sleep Deprivation Disrupts Recall of Conditioned Fear Extinction.

Background: Learned fear is crucial in the development and maintenance of posttraumatic stress disorder (PTSD) and other anxiety disorders, and extinction of learned fear is necessary for response to exposure-based treatments. In humans, research suggests disrupted sleep impairs consolidation of extinction, though no studies have examined this experimentally using total sleep deprivation.

Methods: Seventy-one healthy controls underwent a paradigm to acquire conditioned fear to a visual cue.

HIGH AND LOW THRESHOLD FOR STARTLE REACTIVITY ASSOCIATED WITH PTSD SYMPTOMS BUT NOT PTSD RISK: EVIDENCE FROM A PROSPECTIVE STUDY OF ACTIVE DUTY MARINES.

Background: Heightened startle response is a symptom of PTSD, but evidence for exaggerated startle in PTSD is inconsistent. This prospective study aimed to clarify whether altered startle reactivity represents a trait risk-factor for developing PTSD or a marker of current PTSD symptoms.

Methods: Marines and Navy Corpsmen were assessed before (n = 2,571) and after (n = 1,632) deployments to Iraq or Afghanistan with the Clinician-Administered PTSD Scale (CAPS).

Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder.

Objectives: Affective dysregulation is a core feature of bipolar disorder (BD). Abnormalities in neural circuits underlying affect regulation have been observed in BD, specifically in the structure and function of the amygdala and orbital frontal cortex (OFC). Fear extinction is an automatic affect regulatory process relying on neural circuits that are abnormal in BD.

Early Adolescent Emergence of Reversal Learning Impairments in Isolation-Reared Rats.

Cognitive impairments appear early in the progression of schizophrenia, often preceding the symptoms of psychosis. Thus, the systems subserving these functions may be more vulnerable to, and mechanistically linked with, the initial pathology. Understanding the trajectory of behavioral and anatomical abnormalities relevant to the schizophrenia prodrome and their sensitivity to interventions in relevant models will be critical to identifying early therapeutic strategies.

Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response.

Background: Recent years have seen the emergence of a new paradigm for treatment of anxiety disorders focusing on development of drugs that facilitate psychotherapies via targeted effects on neuroplasticity. One compound that has generated interest in this regard is oxytocin (OT), a mammalian neuropeptide that modulates activity of the neurocircuit mediating fear extinction and memory processes. Recent research in healthy humans has suggested that intranasal OT administered prior to fear extinction training enhances fear extinction performance, supporting its potential to augment exposure-based psychotherapy.

Fear conditioning, safety learning, and sleep in humans.

Fear conditioning is considered an animal model of post-traumatic stress disorder. Such models have shown fear conditioning disrupts subsequent rapid eye movement sleep (REM). Here, we provide a translation of these models into humans.

Sleep deprivation impairs performance in the 5-choice continuous performance test: similarities between humans and mice.

Several groups undergo extended periods without sleep due to working conditions or mental illness. Such sleep deprivation (SD) can deleteriously affect attentional processes and disrupt work and family functioning. Understanding the biological underpinnings of SD effects may assist in developing sleep therapies and cognitive enhancers.